OsteoporosisNCT02629185
The Effects of Obesity on Bone Structure and Strength
An observational study of Osteoporosis and Obesity, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
High body weight is protective against hip and spine fracture, but has been found to increase the risk of humerus, foot and ankle fracture. Increasing understanding of the actions of adipokines on bone suggests that there may be complex effects on different aspects of bone geometry and microarchitecture and that these… Read more about this study
- Who is it for?
- Ages 25 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis, Obesity
- How many people
- 258 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2010to Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy Caucasians Recruited from South Yorkshire, UK
Who may be able to join
- Caucasian
- BMI of 18.5 kg/m2 or above
- Ages 25 to 40 years (and premenopausal if female) or 55 to 75 years (and postmenopausal (at least 5 years since last menstrual period) if female)
- Sufficiently mobile to undergo scanning
- Able to remain motionless for the duration of the scans
- Able and willing to participate in the study and provide written informed consent
Who cannot join
- Previous orthopaedic surgery or fractures which preclude imaging at all sites
- History of any long term immobilization (duration greater than three months)
- High trauma fracture or low trauma fracture less than one year prior to recruitment
- Current pregnancy or trying to conceive
- Delivery of last child less than one year prior to recruitment
- Breast feeding less than one year prior to recruitment
Show all 20Show fewer
- Pre-diagnosed diabetes mellitus
- History of or current conditions known to affect bone metabolism including:
- Diagnosed skeletal disease
- Osteoarthritis at study measurement sites
- Chronic renal disease
- Malabsorption syndromes
- Diagnosed endocrine disorders
- Hypocalcemia or hypercalcemia
- Diagnosed restrictive eating disorder
- Conditions which prevent the analysis of the DXA scans or the interpretation of their result
- Use of medications or treatment known to affect bone metabolism including Depot medroxyprogesterone or the combined oral contraceptive pill
- Alcohol intake of greater than 21 units per week
- Competitive athlete, defined as participating in competitive sport at amateur or professional level
- Markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the PI.
Trial locations and contacts
1 site in 1 country.
About this study
High body weight is protective against hip and spine fracture, but has been found to increase the risk of humerus, foot and ankle fracture. Increasing understanding of the actions of adipokines on bone suggests that there may be complex effects on different aspects of bone geometry and microarchitecture and that these effects may vary depending on whether adipokines act directly on bone cells or through the central nervous system and between cortical and trabecular compartments. Previous research is limited by the use of areal dual-energy x-ray absorptiometry (DXA) scans which may be inaccurate in obese populations due to increased body thickness.
The aim of this study is to investigate the effect of obesity on bone mineral density, bone geometry, bone microarchitecture and bone strength of the hip, lumbar spine, distal radius and tibia.
Read more
This is an observational, cross-sectional study of normal weight and obese individuals matched by age, gender, height, postcode and smoking. The total number of subjects will be 240; men and premenopausal women ages 25 to 40 years and men and postmenopausal women ages 55 to 75 years. DXA, high-resolution peripheral computed tomography (HR-pQCT), quantitative computed tomography (QCT) and finite element analysis will be used to assess bone structure and strength. Biochemical markers of bone turnover and hormones related to bone metabolism will also be measured in order to identify potential mediators of the effects of obesity on bone structure and strength.
A sub-study has been included to evaluate the interaction of fracture risk and cardiovascular risk in obese and non-obese individuals. There is evidence of an interaction between bone mineral density (BMD) and cardiovascular risk and test the hypothesis that there are common pathways linking BMD and cardiovascular risk, including fat secretion of inflammatory cytokines e.g. interleukin-1 and adipokines e.g. leptin and adiponectin. Ultrasound based assessments of vascular function will be used to assess cardiac risk and relate these measures to bone density.
Obese individuals have lower circulating levels of 25OHD. This may be due to poor nutritional intake, reduced sunlight exposure or the vitamin D being stored in fat tissue. The investigators will measure levels of 25OHD in lean, overweight and obese men and women to examine whether 25(OH)D is related to age or gender and whether low 25OHD in obesity affects bone health in subsets of lean, overweight and obese participants of different ages.
Read the detailed description
This is a single centre, observational, cross-sectional, case-controlled study to determine the effects of obesity on bone structure and strength. Cases will be obese individuals and controls will be lean individuals. Overweight individuals will increase the applicability of the vitamin D sub-study to the general population. Cases will be individually matched to controls by gender, age, height, first part of postcode (e.g. S5, S10) and smoking, listed in order of priority. Individually matched controls will reduce the influence of potential confounding factors on the data collected. Blinding is not applicable to this study design.
Participants aged 25-40 years will attend for two visits:
Visit 1 - Consent, questionnaire, anthropometric measurements (height, weight, waist-to-hip ratio (WHR), triceps skinfold), tympanic temperature, blood sampling, neuromuscular function tests (chair stand test, narrow walk test and grip strength) Visit 2 - Anthropometric measurements (height, weight), pregnancy test, measurement of supine abdominal thickness, hip width measurement, DXA (whole body, spine, hip), HR-pQCT (tibia, radius), QCT (spine and hip).
Participants aged 55-75 years will attend for three visits; visits 1 and 2 as for the younger participants, and an additional visit to form the cardiovascular sub-study:
Visit 3 - Anthropometric measurements (height, weight), blood pressure, cardiovascular risk measurements (abdominal aortic calcification (AAC), flow mediated dilatation (FMD), carotid intima-media thickness (CIMT), pulse wave velocity (PWV) and ABPI).
Due to the seasonality of vitamin D levels, the vitamin D sub-study must be completed in the summer months. Participants who have completed the main study prior to August 2012 and have given their consent to be contacted regarding future research will be invited to participate in the vitamin D sub-study by telephone and subsequently sent written information about the vitamin D sub-study. Volunteers will be invited to attend for one additional visit between August 2012 and October 2012.
Future participants (those yet to consent to taking part in the main study) will be invited to participate in the vitamin D sub-study prior to consenting to the main study. As vitamin D levels are affected by seasonality, the substudy components can be completed at visit 1 of the main study for participants who attend for their first study visit between August 2012 and October 2012. However, participants attending for visit 1 of the main study between October 2012 and April 2013 will be invited to attend for an additional visit to complete the vitamin D sub-study in summer/autumn 2013.
Participation in the vitamin D sub-study will require a small blood sample to be taken and the completion of diet and sun exposure questionnaires.
The effect of obesity on bone structure will be determined by comparing the measures of BMD, bone microarchitecture and geometry in the obese study group with the lean group. The effects of obesity on bone strength will be determined using Finite element analysis (FEA). Outcomes from the neuromuscular function tests will be compared between the lean and obese groups to determine the effect of obesity on lower extremity strength, balance, coordination and flexibility. Hormones and bone turnover markers will be compared in lean and obese participants and any associations between hormones and bone turnover markers and measures of bone structure and strength will be identified.
The relationship between cardiovascular risk and BMD will be assessed by comparing the measures of FMD, CIMT, PWV, AAC and ABPI in the obese sub-study group with the lean sub-study group. The interactions between cardiovascular risk and fracture risk will be studies using the surrogate imaging for atherosclerosis risk.
Comparisons of the levels of hormones, inflammatory markers and other biochemical factors will be made between the lean and obese participants and tests will be made for associations between these measures and measures of cardiovascular risk.
The primary outcome in the main study will be mean difference in hip BMD between obese and lean individuals.
Secondary outcomes will be mean difference in cross-sectional moment of inertia, cortical and trabecular BMD, bone microarchitecture and geometry and neuromuscular function between lean and obese individuals, association between BMD and cardiovascular risk and association between body weight and circulating 25(OH)D.
- Conditions
- Osteoporosis, Obesity
- Keywords
- Bone, Vitamin D, Cardiovascular
- Medical subject headings
- Osteoporosis, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| normal weight | BMI 18.5 to 25.0 Healthy men and women ages 25-40 and 55-75 | |
| overweight | BMI 25.0 to 30.0 Healthy men and women ages 25-40 and 55-75 | |
| obese | BMI over 30.0 Healthy men and women ages 25-40 and 55-75 |
What is being measured
The primary outcome is the main question the study is designed to answer.
mean difference in DXA hip BMD between normal weight and obese
Measured: one measurement at study entry (cross-sectional study)
Secondary outcomes (6)
mean difference in other BMD measures between normal weight and obese
DXA spine and hip, QCT spine and hip, HR-pQCT radius and tibia
Measured: one measurement at study entry (cross-sectional study)
mean difference in bone microarchitecture measures between normal weight and obese
HR-pQCT radius and tibia
Measured: one measurement at study entry (cross-sectional study)
mean difference in biochemical bone turnover markers between normal weight and obese
serum C-terminal crosslink of type I collagen (CTX), n-teminal telopeptide of type I procoallgen (PINP), osteocalcin, bone alkaline phosphatase (BAP)
Measured: one measurement at study entry (cross-sectional study)
mean difference in hormones between normal weight and obese
sex steroids, insulin-like growth hormone -1 (IGF-1), adipocyte hormones
Measured: one measurement at study entry (cross-sectional study)
mean difference in cardiovascular risk measures between normal weight and obese
lipids, CIMT, PWV, AAC, FMD
Measured: one measurement at study entry (cross-sectional study)
mean difference in vitamin D measures between normal weight and obese
25OHD, 1,25OHD, DBP, free 25OHD, vitamin D binding protein (DBP), DBP genotype
Measured: one measurement at study entry (cross-sectional study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2015 (estimated)
- Study startSep 2010
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
- Enrolment
- 258 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sheffield, National Osteoporosis Society, Orthopaedic Research UK
- Responsible party
- Sponsor
- Investigators
- Jennifer S Walsh, MBChB PhD, Principal investigator, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02629185
- Sponsor's protocol ID
- STH15688
- Status last verified
- Dec 2015
- First submitted
- 7 Dec 2015
- Last updated
- 14 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. 2015 May;30(5):920-8. doi: 10.1002/jbmr.2407.
PubMed 25400253
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Obesity on Bone Structure and Strength
- ClinicalTrials.gov ID
- NCT02629185
- Acronym / sponsor ID
- STH15688
- Conditions
- Osteoporosis, Obesity
- Keywords
- Bone, Vitamin D, Cardiovascular
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 258 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Sheffield, National Osteoporosis Society, Orthopaedic Research UK
- Study start
- Sep 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 14 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High body weight is protective against hip and spine fracture, but has been found to increase the risk of humerus, foot and ankle fracture. Increasing understanding of the actions of adipokines on bone suggests that there may be complex effects on different aspects of bone geometry and microarchitecture and that these effects may vary depending on whether adipokines act directly on bone cells or through the central nervous system and between cortical and trabecular compartments. Previous research is limited by the use of areal dual-energy x-ray absorptiometry (DXA) scans which may be inaccurate in obese populations due to increased body thickness.
The aim of this study is to investigate the effect of obesity on bone mineral density, bone geometry, bone microarchitecture and bone strength of the hip, lumbar spine, distal radius and tibia.
This is an observational, cross-sectional study of normal weight and obese individuals matched by age, gender, height, postcode and smoking. The total number of subjects will be 240; men and premenopausal women ages 25 to 40 years and men and postmenopausal women ages 55 to 75 years. DXA, high-resolution peripheral computed tomography (HR-pQCT), quantitative computed tomography (QCT) and finite element analysis will be used to assess bone structure and strength. Biochemical markers of bone turnover and hormones related to bone metabolism will also be measured in order to identify potential mediators of the effects of obesity on bone structure and strength.
A sub-study has been included to evaluate the interaction of fracture risk and cardiovascular risk in obese and non-obese individuals. There is evidence of an interaction between bone mineral density (BMD) and cardiovascular risk and test the hypothesis that there are common pathways linking BMD and cardiovascular risk, including fat secretion of inflammatory cytokines e.g. interleukin-1 and adipokines e.g. leptin and adiponectin. Ultrasound based assessments of vascular function will be used to assess cardiac risk and relate these measures to bone density.
Obese individuals have lower circulating levels of 25OHD. This may be due to poor nutritional intake, reduced sunlight exposure or the vitamin D being stored in fat tissue. The investigators will measure levels of 25OHD in lean, overweight and obese men and women to examine whether 25(OH)D is related to age or gender and whether low 25OHD in obesity affects bone health in subsets of lean, overweight and obese participants of different ages.
Detailed description
This is a single centre, observational, cross-sectional, case-controlled study to determine the effects of obesity on bone structure and strength. Cases will be obese individuals and controls will be lean individuals. Overweight individuals will increase the applicability of the vitamin D sub-study to the general population. Cases will be individually matched to controls by gender, age, height, first part of postcode (e.g. S5, S10) and smoking, listed in order of priority. Individually matched controls will reduce the influence of potential confounding factors on the data collected. Blinding is not applicable to this study design.
Participants aged 25-40 years will attend for two visits:
Visit 1 - Consent, questionnaire, anthropometric measurements (height, weight, waist-to-hip ratio (WHR), triceps skinfold), tympanic temperature, blood sampling, neuromuscular function tests (chair stand test, narrow walk test and grip strength) Visit 2 - Anthropometric measurements (height, weight), pregnancy test, measurement of supine abdominal thickness, hip width measurement, DXA (whole body, spine, hip), HR-pQCT (tibia, radius), QCT (spine and hip).
Participants aged 55-75 years will attend for three visits; visits 1 and 2 as for the younger participants, and an additional visit to form the cardiovascular sub-study:
Visit 3 - Anthropometric measurements (height, weight), blood pressure, cardiovascular risk measurements (abdominal aortic calcification (AAC), flow mediated dilatation (FMD), carotid intima-media thickness (CIMT), pulse wave velocity (PWV) and ABPI).
Due to the seasonality of vitamin D levels, the vitamin D sub-study must be completed in the summer months. Participants who have completed the main study prior to August 2012 and have given their consent to be contacted regarding future research will be invited to participate in the vitamin D sub-study by telephone and subsequently sent written information about the vitamin D sub-study. Volunteers will be invited to attend for one additional visit between August 2012 and October 2012.
Future participants (those yet to consent to taking part in the main study) will be invited to participate in the vitamin D sub-study prior to consenting to the main study. As vitamin D levels are affected by seasonality, the substudy components can be completed at visit 1 of the main study for participants who attend for their first study visit between August 2012 and October 2012. However, participants attending for visit 1 of the main study between October 2012 and April 2013 will be invited to attend for an additional visit to complete the vitamin D sub-study in summer/autumn 2013.
Participation in the vitamin D sub-study will require a small blood sample to be taken and the completion of diet and sun exposure questionnaires.
The effect of obesity on bone structure will be determined by comparing the measures of BMD, bone microarchitecture and geometry in the obese study group with the lean group. The effects of obesity on bone strength will be determined using Finite element analysis (FEA). Outcomes from the neuromuscular function tests will be compared between the lean and obese groups to determine the effect of obesity on lower extremity strength, balance, coordination and flexibility. Hormones and bone turnover markers will be compared in lean and obese participants and any associations between hormones and bone turnover markers and measures of bone structure and strength will be identified.
The relationship between cardiovascular risk and BMD will be assessed by comparing the measures of FMD, CIMT, PWV, AAC and ABPI in the obese sub-study group with the lean sub-study group. The interactions between cardiovascular risk and fracture risk will be studies using the surrogate imaging for atherosclerosis risk.
Comparisons of the levels of hormones, inflammatory markers and other biochemical factors will be made between the lean and obese participants and tests will be made for associations between these measures and measures of cardiovascular risk.
The primary outcome in the main study will be mean difference in hip BMD between obese and lean individuals.
Secondary outcomes will be mean difference in cross-sectional moment of inertia, cortical and trabecular BMD, bone microarchitecture and geometry and neuromuscular function between lean and obese individuals, association between BMD and cardiovascular risk and association between body weight and circulating 25(OH)D.
Study design
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| normal weight | – | –BMI 18.5 to 25.0 Healthy men and women ages 25-40 and 55-75 |
| overweight | – | –BMI 25.0 to 30.0 Healthy men and women ages 25-40 and 55-75 |
| obese | – | –BMI over 30.0 Healthy men and women ages 25-40 and 55-75 |
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy Caucasians Recruited from South Yorkshire, UK
Key inclusion criteria (6 listed)
- Caucasian
- BMI of 18.5 kg/m2 or above
- Ages 25 to 40 years (and premenopausal if female) or 55 to 75 years (and postmenopausal (at least 5 years since last menstrual period) if female)
- Sufficiently mobile to undergo scanning
- Able to remain motionless for the duration of the scans
Key exclusion criteria (20 listed)
- Previous orthopaedic surgery or fractures which preclude imaging at all sites
- History of any long term immobilization (duration greater than three months)
- High trauma fracture or low trauma fracture less than one year prior to recruitment
- Current pregnancy or trying to conceive
- Delivery of last child less than one year prior to recruitment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
mean difference in DXA hip BMD between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
6 secondary outcomes
mean difference in other BMD measures between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
mean difference in bone microarchitecture measures between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
mean difference in biochemical bone turnover markers between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
mean difference in hormones between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
mean difference in cardiovascular risk measures between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
mean difference in vitamin D measures between normal weight and obese
Time frame: one measurement at study entry (cross-sectional study)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2015.
- Results publication: PubMed 25400253Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. 2015 May;30(5):920-8. doi: 10.1002/jbmr.2407.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer S Walsh, MBChB PhD principal investigator
University of Sheffield
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteoporosis and Obesity, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mean difference in DXA hip BMD between normal weight and obese (time frame: one measurement at study entry (cross-sectional study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02629185, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2015.